A multidisciplinary team of scientists, nanotechnologists and physicians will establish a Program of Excellence in Nanotechnology (PEN), with the central focus being research and educational activities related to "Integrated Nanosystems for Diagnosis and Therapy". This PEN will include investigators from the Schools of Arts &Sciences and Medicine at Washington University, as well as nanotechnologists from the University of California campuses at Berkeley and Santa Barbara. The central mission is the development of a group of well-characterized and versatile nanoscale agents that can be assembled, labeled, targeted, filled, and activated as needed for the combined purposes of diagnosis and treatment of various diseases of relevance to NHLBI. The overall experimental strategy will focus on biological models of acute pulmonary and systemic vascular Injury (in vitro and in vivo) to demonstrate the effectiveness of these agents. There are six specific aims for this PEN: (1) Preparation and assembly of programmed, integrated nanosystems;(2) Application of nanostructures for imaging at increased levels of sensitivity;(3) Imaging of gene expression by recognition of mRNA transcription products;(4) Application of the nanostructures for therapy;(5) Cross disciplinary education and training of medical and materials scientists, and;(6) Dissemination and translation of nanotechnology developments. Fundamental studies will be conducted to understand the potential roles and limitations for nanotechnology as applied to medicine, and a number of applied studies will work toward the implementation of well-defined nanostructures for diagnosis and treatment of acute vascular injury and inflammation, with validation in the lung and cardio-vasculature. General methodologies will be developed for the preparation and characterization of novel plurifunctional nanostructures that can serve as hosts for both diagnostic and therapeutic agents, and then be destroyed safely once they have fulfilled their function (Aim 1). Demonstration of enhanced imaging capabilities will be performed for radio-, MR- and optically-labeled nanostructures by positron emission tomography, magnetic resonance and optical imaging, respectively, whereby tissues are targeted via ligands for cell surface receptors (Aim 2). Intracellular targeting will also be developed to allow for identification and "reading" of mRNA, as a means to perform direct Imaging of gene products that are either unregulated in a disease state or that are the products of gene transfer (Aim 3). It is expected that these new approaches will be applicable generally as a new form of molecular imaging that eliminates the need for reporter genes. In addition to the imaging of acute vascular injury, treatment by the delivery of various therapeutic agents using an array of nanoscale materials will be developed (Aim 4). Critical to the success of this PEN will be the establishment of infrastructure for the education, training and mentoring of students and postdoctorals, through formal course, workshops and laboratory rotations (Aim 5), and to the establishment of an affective and broadly based mechanism for dissemination of results, procedures and programs (Aim 6). Through these initiatives, we will provide leadership for the development of nanoscience and nanotechnology that can impact clinical directives and capabilities through the 21st century.